1. Field of the Invention
The present invention relates to new industrial processes for the preparation of vitamin K derivatives, which play an important role in the vital body as hematostatic vitamins, and intermediates useful for the preparation thereof.
2. Description of the Background Art
Naphthoquinone derivatives, which are vitamin K derivatives, have heretofore been prepared by reacting 2-methyl-1,4-naphthoquinone (menadione) or the like with an allyl halide derivative by the Friedel-Crafts reaction.
Besides, Japanese Patent Application Laid-Open (KOKAI) No. 56935/1985 discloses a process for preparing a naphthoquinone derivative by forming 1,4,4.sub.a .alpha.,9.sub.a -tetrahydro-9.sub.a .alpha.-methyl-1.alpha.,4.alpha.-methanoanthraquinone from 2-methyl-1,4-naphthoquinone and cyclopentadiene, reacting this product with an allyl halide derivative into a 1,4,4.sub.a .alpha.,9.sub.a -tetrahydro-9.sub.a .alpha.-methyl-4.sub.a .alpha.-alkenyl-1.alpha.,4.alpha.-methanoanthraquinone, and then refluxing the thus-obtained product under heat in a toluene solvent to conduct a Retro Dieis-Alder reaction. In the conventional processes for preparing naphthoquinone derivatives, 2-methyl-1,4-naphthoquinone which is a starting material has been extremely expensive and hence difficult to obtain in a great amount on an industrial scale. Further, naphthoquinone derivatives produced by conducting the Friedel-Crafts reaction undergo geometric isomerization on the allyl group as indicated by the following chemical reaction formula. Therefore, the final product is provided as a mixture of an intended trans (E) isomer and a cis (Z) isomer formed as a by-product. In addition, they are very difficult to separate from each other to purify them because their physicochemical properties are similar to each other. Accordingly, this process has not been said to be an industrially or economically satisfactory process. ##STR2##
On the other hand, the process disclosed in Japanese Patent Application Laid-Open (KOKAI) No. 56935/1985 can improve the disadvantage that the geometric isomers are formed, but has remained using 2-methyl-1,4-naphthoquinone as a starting material. Therefore, a problem has remained unsolved from the viewpoint of obtaining the starting material.
In addition, the process disclosed in Japanese Patent Application Laid-Open (KOKAI) No. 56935/1985 requires a strong base such as a metal amide, lithium dialkylamide, alkali metal t-butyrate, sodium hydride or potassium hydride for the reaction of 1,4,4.sub.a .alpha.,9.sub.a -tetrahydro-9.sub.a .alpha.-methyl-1.alpha.,4.alpha.-methanoanthraquinone or the like with an allyl halide derivative. However, these strong bases are materials difficult to industrially handle in a great amount from the viewpoint of flammability, corrosiveness, decomposition behavior due to moisture absorption, toxicity, shelf stability and the like. This process has not been said to be always an industrially suitable process.
1,4,4.sub.a .alpha.,9.sub.a -Tetrahydro-9.sub.a .alpha.-methyl-1,.alpha.,4.alpha.-methanoanthraquinone or the like, which is a starting material in the above publication, is obtained by the Dieis-Alder reaction of 2-methyl-1,4-naphthoquinone, 2,3-dimethoxy-5-methylbenzoquinone or the like with cyclopentadiene. However, this addition reaction is extremely slow, and it takes four long days to complete the reaction as described in Examples of the above publication. Such a process has hence been disadvantageous from the industrial viewpoint.
As described above, the disadvantage of forming the geometric isomers, the problem from the viewpoint of obtaining starting materials, the difficulty of handling the bases, or the time problem involved in the preparation of the starting material has not been yet solved in the conventionally-known processes. Therefore, such processes all have been insufficient for industrial processes. With such a background, there has been demand for development of an industrially excellent preparation process for naphthoquinone derivatives, by which an intended naphthoquinone derivative can be prepared from cheap and easily available starting materials with good operating simplicity for a short period of time without forming any geometric isomer.